Objectives:To describe the phenoty pe of Leber congenital amaurosis(LCA)in 26probands with mutations in aryl hydrocarbon receptor interacting p rotein-like 1protein(AIPL1)and compare it with phenotypes of oth er LCA-related genes.To describe the e lectroretinogram(ERG)in heterozygote carriers.Methods:Patients with AIPL1-related LCA were identified i n a cohort of 303pa-tients with LCA by polymerase chain r eaction single-strand confirmational polymorphism mutation screening and /or direct sequencing.Phenotypic characterization included clinical and ERG evaluation.Seven h eterozygous carrier parents also underwent ERG testing.Results:Seventeen homozygotes and 9compound heterozy gotes were identi-fied.The W278X mutation was most fre quent (48%of alleles).Visual acuities ranged from light p erception to20/400.Variable retinal appearances,ranging from near normal to varying degrees of chorioretinal atrophy and in-traretinal pigment migration,were noted.Atrophic and /or pigmentary macular changes were pre sent in 16(80%)of20probands.Keratoconus and catara cts were identified in5(26%)of 19patients,all of whom were homozygotes.The ERG of a parent heterozygote carrier revealed signifi-cantly reduced rod function,while ERGs for 6other carrier parents were normal.Conclusions:T he phenotype of LCA in patients with AIPL1mutations is r elatively severe,with a maculopathy in most patients and keratoconus and cataract in a large subset.Rod ERG ab normalities may be present in heterozygous carriers of AIPL1mutations.Clin-ical Relevance:Understanding and r ecognizing the pheno-type of LCA may help in defining the co urse and severity of the disease.Identifying the gene defect is the first step in preparation for therapy since molec ular diagnosis in LCA will mandate the choice of treatment . Objectives: To describe the phenoty pe of Leber congenital amaurosis (LCA) in 26probands with mutations in aryl hydrocarbon receptor interacting p rotein-like 1 protein (AIPL1) and compare it with phenotypes of oth er LCA-related genes. To describe the e lectroretinogram ( ERG) in heterozygote carriers. Methods: Patients with AIPL1-related LCA were identified in a cohort of 303 pa-tients with LCA by polymerase chain r eaction single-strand confirmational polymorphism mutation screening and / or direct sequencing. Phenotypic characterization included clinical and ERG evaluation. Seven hterozygous carrier parents also underwent ERG testing. Results: Seventeen homozygotes and 9 compounded heterozy gotes were identi-fied. The W278X mutation was most fre quent (48% of alleles) .Visual acuities ranged from light p erception to 20/400. Variable retinal appearances, ranging from near normal to varying degrees of chorioretinal atrophy and in-traretinal pigment migration, were noted. Atrophic and / or pigmentary macular c hanges were pre sent in 16 (80%) of 20probands.Keratoconus and catara cts were identified in5 (26%) of 19patients, all of whom were homozygotes.The ERG of a parent heterozygote carrier revealed signifi-cantly reduced rod function, while ERGs for 6other carrier parents were normal. Conclusions: T he phenotype of LCA in patients with AIPL1mutations is r elatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset. Rod ERG ab normalities may be present in heterozygous carriers of AIPL1mutations. Clin-ical Relevance: Understanding and r ecognizing the pheno-type of LCA may help in defining the co urse and severity of the disease. Identifying the gene defect is the first step in preparation for therapy because molec ular diagnosis in LCA will mandate the choice of treatment.